Hydrogen Bromide → Quinoline

The 5-trifluoromethyl-8-methoxyquinoline 8.50 g was dissolved in 100 mL glacial acetic acid and added to 20 ml HBr in a 100 mL flask. The solution was heated to reflux for 20 hrs. The reaction mixture was allowed to come to room temperature. The reaction mixture was concentrated by removal of 55 mL of solvent under vacuum. The solution was then poured into 100 mL cold water and neutralized with 2N NaOH to pH 7.0. The resulting solution was extracted with 2×100 ml ether, dried with NaSO4, filtered and concentrated to an oil, which solidified upon standing (5.0 g). The crude material was purified by filtration through a short silica gel column where the silica was first washed with 2% TEA in methylene chloride. The column was then dried under N2 pressure and re-solvated with neat methylene chloride. Elution with 2% EtOH/methylene chloride gave 1.41 g of the desired product as a white crystalline solid.

1. temperatureThe solution was heated
2. temperatureto reflux for 20 hrs
3. customto come to room temperature
4. concentrationThe reaction mixture was concentrated by removal of 55 mL of solvent under vacuum
5. additionThe solution was then poured into 100 mL cold water and neutralized with 2N NaOH to pH 7.0
6. extractionThe resulting solution was extracted with 2×100 ml ether
7. dry with materialdried with NaSO4
8. filtrationfiltered
9. concentrationconcentrated to an oil, which
10. filtrationThe crude material was purified by filtration through a short silica gel column where the silica
11. washwas first washed with 2% TEA in methylene chloride
12. customThe column was then dried under N2 pressure
13. washElution with 2% EtOH/methylene chloride

ORD record

ord-f7758520d6aa4ebb9a9d8d33a3b98139

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07230107B1